Non-human primate-derived pan-ebola and pan-filovirus monoclonal antibodies directed against envelope glycoproteins

Abstract

The disclosure provides non-human primate-derived binding molecules, e.g., antibodies or antigen-binding fragments thereof, that can bind to orthologous epitopes found on two or more filovirus species or strains.

What is claimed is: 
     
       1. An isolated antibody or antigen-binding fragment thereof comprising a binding domain that specifically binds to a filovirus glycoprotein epitope, wherein the binding domain comprises VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences identical to SEQ ID NOs: 33, 34, 35, 38, 39, and 40, respectively. 
     
     
       2. The antibody or antigen-binding fragment thereof of  claim 1 , wherein the binding domain comprises heavy chain variable region (VH) and light chain variable region (VL) amino acid sequences comprising SEQ ID NO: 32 and SEQ ID NO: 37, respectively. 
     
     
       3. The antibody or antigen-binding fragment thereof of  claim 1  which is a non-human primate (NHP) antibody, a humanized antibody, a chimeric antibody, or a fragment thereof. 
     
     
       4. The antibody or antigen-binding fragment thereof of  claim 1 , which is a monoclonal antibody, a component of a polyclonal antibody mixture, a recombinant antibody, a multispecific antibody, or any combination thereof. 
     
     
       5. The antibody or antigen-binding fragment thereof of  claim 1 , comprising an Fv fragment, an Fab fragment, an F(ab′)2 fragment, an Fab′ fragment, a dsFv fragment, an scFv fragment, an scFab fragment, an sc(Fv)2 fragment, or any combination thereof. 
     
     
       6. The antibody or antigen-binding fragment thereof of  claim 1 , wherein binding of the binding domain to the epitope on a filovirus fully or partially neutralizes infectivity of the filovirus. 
     
     
       7. The antibody or antigen-binding fragment thereof of  claim 1 , which is conjugated to an antiviral agent, a protein, a lipid, a detectable label, a polymer, or any combination thereof. 
     
     
       8. A composition comprising the antibody or antigen-binding fragment thereof of  claim 1 , and a carrier. 
     
     
       9. A method of making the antibody or antigen-binding fragment thereof of  claim 1 , comprising:
 (a) culturing a host cell wherein the host cell comprises a vector comprising an isolated polynucleotide or a combination of polynucleotides encoding the antibody or antigen-binding fragment thereof of  claim 1 ; and 
 (b) isolating and purifying the antibody or fragment thereof. 
 
     
     
       10. The isolated antibody or antigen-binding fragment thereof of  claim 1 , wherein the binding domain specifically binds to the epitope on two or more filovirus species or strains. 
     
     
       11. The isolated antibody or antigen-binding fragment thereof of  claim 1 , wherein the binding domain is derived from a non-human primate (NHP) antibody.